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Study of the NR 4A family gene expression in patients with multiple sclerosis treated with Fingolimod
Author(s) -
Montarolo F.,
Perga S.,
Martire S.,
Brescia F.,
Caldano M.,
Lo Re M.,
Panzica G.,
Bertolotto A.
Publication year - 2019
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13875
Subject(s) - fingolimod , multiple sclerosis , medicine , pathogenesis , relapsing remitting , gene expression , immune system , gene , immunology , pharmacology , biochemistry , chemistry
Background and purpose Fingolimod is a drug approved for treatment of relapsing‐remitting multiple sclerosis ( RRMS ) that exerts its effects via sequestering lymphocytes within the lymph nodes. The drug, acting on the sphingosine‐1‐phosphate pathway, is involved in a plethora of processes and, to date, its mechanism of action is not completely understood. Recently, it has been demonstrated that Fingolimod increases the expression of transcription factor NR 4A2 in murine brain. NR 4A2 belongs to nuclear receptor family 4, group A ( NR 4A) along with NR 4A1 and NR 4A3. The role of NR 4A2 in the pathogenesis of multiple sclerosis is already known and supported by its down‐regulation observed in blood obtained from patients with RRMS compared with healthy controls ( HCs ). It is notable that NR 4A2 impairment is reversed in patients with RRMS during pregnancy, which represents a transitory state of immune tolerance, associated with reduced disease activity. An inverse correlation between NR 4A2 gene expression levels and clinical parameters indicates that more aggressive forms of the disease are characterized by lower levels of NR 4A2. Methods Gene expression levels of NR 4A in blood obtained from HCs , treatment‐naive (T0) and Fingolimod‐treated patients with RRMS were evaluated to determine their contribution to drug response. Results Gene expression levels of NR 4A were down‐regulated in T0 patients compared with HCs . Patients treated with Fingolimod for >2 years were characterized by higher levels of NR 4A2 compared with the T0 group, approaching those of HCs . NR 4A1 and NR 4A3 levels were not altered. Conclusions Involvement of the NR 4A family in the pathogenesis of multiple sclerosis and a role of Fingolimod in the recovery from NR 4A2 deficit can be hypothesized based on our data.